Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25091 | 75496;75497;75498 | chr2:178570861;178570860;178570859 | chr2:179435588;179435587;179435586 |
| N2AB | 23450 | 70573;70574;70575 | chr2:178570861;178570860;178570859 | chr2:179435588;179435587;179435586 |
| N2A | 22523 | 67792;67793;67794 | chr2:178570861;178570860;178570859 | chr2:179435588;179435587;179435586 |
| N2B | 16026 | 48301;48302;48303 | chr2:178570861;178570860;178570859 | chr2:179435588;179435587;179435586 |
| Novex-1 | 16151 | 48676;48677;48678 | chr2:178570861;178570860;178570859 | chr2:179435588;179435587;179435586 |
| Novex-2 | 16218 | 48877;48878;48879 | chr2:178570861;178570860;178570859 | chr2:179435588;179435587;179435586 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/G | rs886609420  |
-1.655 | 0.892 | N | 0.689 | 0.238 | 0.141422826196 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| S/G | rs886609420 |
-1.655 | 0.892 | N | 0.689 | 0.238 | 0.141422826196 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| S/G | rs886609420 |
-1.655 | 0.892 | N | 0.689 | 0.238 | 0.141422826196 | gnomAD-4.0.0 | 3.71881E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.08636E-06 | 0 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.6234 | likely_pathogenic | 0.6032 | pathogenic | -0.685 | Destabilizing | 0.818 | D | 0.68 | prob.neutral | None | None | None | None | N |
| S/C | 0.7329 | likely_pathogenic | 0.7151 | pathogenic | -0.58 | Destabilizing | 0.999 | D | 0.785 | deleterious | D | 0.532715306 | None | None | N |
| S/D | 0.9938 | likely_pathogenic | 0.9941 | pathogenic | -1.199 | Destabilizing | 0.957 | D | 0.735 | prob.delet. | None | None | None | None | N |
| S/E | 0.9964 | likely_pathogenic | 0.9965 | pathogenic | -1.108 | Destabilizing | 0.916 | D | 0.699 | prob.neutral | None | None | None | None | N |
| S/F | 0.9955 | likely_pathogenic | 0.9958 | pathogenic | -0.525 | Destabilizing | 0.996 | D | 0.872 | deleterious | None | None | None | None | N |
| S/G | 0.3671 | ambiguous | 0.3623 | ambiguous | -1.025 | Destabilizing | 0.892 | D | 0.689 | prob.neutral | N | 0.471524509 | None | None | N |
| S/H | 0.9904 | likely_pathogenic | 0.9904 | pathogenic | -1.513 | Destabilizing | 0.997 | D | 0.788 | deleterious | None | None | None | None | N |
| S/I | 0.9926 | likely_pathogenic | 0.9926 | pathogenic | 0.141 | Stabilizing | 0.983 | D | 0.873 | deleterious | D | 0.532968796 | None | None | N |
| S/K | 0.9991 | likely_pathogenic | 0.9991 | pathogenic | -0.838 | Destabilizing | 0.845 | D | 0.688 | prob.neutral | None | None | None | None | N |
| S/L | 0.944 | likely_pathogenic | 0.9455 | pathogenic | 0.141 | Stabilizing | 0.916 | D | 0.84 | deleterious | None | None | None | None | N |
| S/M | 0.9792 | likely_pathogenic | 0.9789 | pathogenic | 0.264 | Stabilizing | 0.999 | D | 0.79 | deleterious | None | None | None | None | N |
| S/N | 0.9775 | likely_pathogenic | 0.9772 | pathogenic | -1.134 | Destabilizing | 0.892 | D | 0.718 | prob.delet. | D | 0.531701348 | None | None | N |
| S/P | 0.9879 | likely_pathogenic | 0.9894 | pathogenic | -0.098 | Destabilizing | 0.996 | D | 0.823 | deleterious | None | None | None | None | N |
| S/Q | 0.9943 | likely_pathogenic | 0.9943 | pathogenic | -1.096 | Destabilizing | 0.975 | D | 0.751 | deleterious | None | None | None | None | N |
| S/R | 0.9977 | likely_pathogenic | 0.9978 | pathogenic | -0.929 | Destabilizing | 0.056 | N | 0.633 | neutral | D | 0.531954838 | None | None | N |
| S/T | 0.7348 | likely_pathogenic | 0.7324 | pathogenic | -0.909 | Destabilizing | 0.892 | D | 0.689 | prob.neutral | N | 0.520433948 | None | None | N |
| S/V | 0.9854 | likely_pathogenic | 0.9848 | pathogenic | -0.098 | Destabilizing | 0.987 | D | 0.847 | deleterious | None | None | None | None | N |
| S/W | 0.9938 | likely_pathogenic | 0.9944 | pathogenic | -0.691 | Destabilizing | 0.999 | D | 0.86 | deleterious | None | None | None | None | N |
| S/Y | 0.9926 | likely_pathogenic | 0.9929 | pathogenic | -0.349 | Destabilizing | 0.996 | D | 0.873 | deleterious | None | None | None | None | N |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.